Benzodiazepines, e.g., diazepam and flunitrazepam, have been widely known as anxiolytic agents acting on the central nervous system (CNS) of man. Recent studies have led to the following observations and conclusions:
(1) Benzodiazepines bind selectively and stereospecifically to particular receptors of brain tissues, especially those located in the cortical regions. Because of this important and well-known discovery, these receptors have been designated as "benzodiazepine receptors."
(2) It has been established that the binding ability of benzodiazepines to these specific receptors in the central nervous system correlates closely with their anxiolytic activity.
(3) Tritium-labelled diazepam (.sup.3 H-diazepam) of known activity has been used successfully as a label for the benzodiazepine receptors due to its highly efficient and specific binding with the receptors. Since the ability to bind or to compete for the benzodiazepine receptors by a chemical compound parallels its efficacy as an anxiolytic, anticonvulsant or hypnotic agent, the effect of the compound on the .sup.3 H-diazepam binding has been measured and used in bioassays for the discovery and/or evaluation of antagonists or agonists of the benzodiazepine receptors.
(4) It is known that tracazolate, a known anxiolytic/analgesic also stimulates benzodiazepine binding.
This invention relates to, among other compounds, 3',6-diisopentenyl-2',4'-dihydroxy-5,7-dimethoxyisoflavan which is a potent stimulator to the benzodiazepine receptors and is useful as a minor tranquilizer or a sleeping pill. It is also a potent antidote for various CNS-acting insecticides including (S) .alpha.-cyano-3-phenoxybenzyl pyrethroid and avermectin which is also a highly effective antibiotic and antiparasitic agent for mammals.
3',6-Diisopentenyl-2',4'-dihydroxy-5,7-dimethoxyisoflavan has been isolated from a methylene chloride extract of Glycyrrhiza uralensis Fisch. The dried rhizomes and roots of the genus Glycyrrhiza (leguminosae), known as "licorice", have been explored as herbal medicine for peptic ulcer and pharangeal irritation or cough in Asia and Europe.
Accordingly, it is the object of the present invention to provide pure 3',6-diisopentenyl-2',4'-dihydroxy-5,7-dimethoxyisoflavan which is useful as a specific stimulator of benzodiazepine receptors and an antidote for avermectin.
Another object of this invention is to provide processes for the isolation and purification of this novel compound.
A further object of this invention is to provide a pharmaceutically acceptable composition containing 3',6-diisopentenyl-2',4'-dihydroxy-5,7-dimethoxyisoflavan and/or one or more of other active compounds for the treatment of anxiety, intoxication by avermectin and other CNS disorders controlled by the benzodiazepine receptors.
Still a further object of this invention is to provide a method of treatment involving the administration of a therapeutically effective amount of these benzodiazepine receptor stimulators to a patient suffering from various CNS disorders including, for example, anxiety, insomnia, and intoxication caused by CNS-acting insecticides and/or antiparasitic agents such as avermectin.